Protein lactylation, an emerging post-translational modification, is providing new insights into tumor biology and challenging our current understanding of cancer mechanisms. Our review illuminates the intricate roles of lactylation in carcinogenesis, tumor progression, and therapeutic responses, positioning it as a critical linchpin connecting metabolic reprogramming, epigenetic modulation, and treatment outcomes. We provide an in-depth analysis of lactylation's molecular mechanisms and its far-reaching impact on cell cycle regulation, immune evasion strategies, and therapeutic resistance within the complex tumor microenvironment. Notably, this review dissects the paradoxical nature of lactylation in cancer immunotherapy and radiotherapy. While heightened lactylation can foster immune suppression and radioresistance, strategically targeting lactylation cascades opens innovative avenues for amplifying the efficacy of current treatment paradigms. We critically evaluate lactylation's potential as a robust diagnostic and prognostic biomarker and explore frontier therapeutic approaches targeting lactylation. The synergistic integration of multi-omics data and artificial intelligence in lactylation research is catalyzing significant strides towards personalized cancer management. This review not only consolidates current knowledge but also charts a course for future investigations. Key research imperatives include deciphering tumor-specific lactylation signatures, optimizing synergistic strategies combining lactylation modulation with immune checkpoint inhibitors and radiotherapy, and comprehensively assessing the long-term physiological implications of lactylation intervention. As our understanding of lactylation's pivotal role in tumor biology continues to evolve, this burgeoning field promises to usher in transformative advancements in cancer diagnosis, treatment modalitie.
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http://dx.doi.org/10.1016/j.arr.2025.102670 | DOI Listing |
Cell Metab
January 2025
Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, 410008 Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 410008 Changsha, Hunan, China; FuRong Laboratory, 410078 Changsha, Hunan, China. Electronic address:
The benefits of exercise for metabolic health occur in a dose-dependent manner. However, the adverse effects of overtraining and their underlying mechanisms remain unclear. Here, we show that overtraining induces hepatic fibrosis.
View Article and Find Full Text PDFFront Cell Neurosci
January 2025
Hainan General Hospital and Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
Protein lactylation is a new form of post-translational modification that has recently been proposed. Lactoyl groups, derived mainly from the glycolytic product lactate, have been linked to protein lactylation in brain tissue, which has been shown to correlate with increased neuronal excitability. Ischemic stroke may promote neuronal glycolysis, leading to lactate accumulation in brain tissue.
View Article and Find Full Text PDFClin Sci (Lond)
January 2025
School of Basic Medicine, Health Science Center, Yangtze University, Nanhuan Road 1, Jingzhou, Hubei 434023, China.
Lactylation, a post-translational modification, has been linked to gene transcription regulation through epigenetic modulation in various pathophysiological processes. The lactylation regulatory proteins, known as writers, erasers, and readers, govern their dynamics by adding, removing, and recognizing lactyl groups on proteins. Macrophages, as cells of the immune system, maintain homeostasis, responding dynamically to diverse internal and external stimuli.
View Article and Find Full Text PDFLife Metab
June 2024
Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200438, China.
Front Oncol
January 2025
Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
Background: Recent research has highlighted lactate's crucial role in epigenetic regulation, particularly by influencing histone modifications that drive the initiation and progression of hepatocellular carcinoma (HCC). While mitochondria are known to regulate tumor behavior, the interaction between lactate metabolism and mitochondrial function in cancer tissues remains underexplored. Understanding this relationship may provide deeper insights into tumor metabolic reprogramming and reveal novel therapeutic targets for HCC and other malignancies.
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